CHUGAI-PHARMACEUTICAL

Chugai
Pharmaceutical Co., Ltd.
(TOKYO:4519) today announced that full
results from HAVEN 3 study (NCT02847637) and HAVEN 4 study (NCT03020160)
evaluating Chugai’s hemophilia A treatment HEMLIBRA®
[generic
name: emicizumab (genetical recombination)] are being presented at the
World Federation of Hemophilia 2018 World Congress held in Glasgow,
Scotland from May 20 to 24. HAVEN 3 study is conducted in people with
hemophilia A without inhibitors, and HAVEN 4 study is conducted in
people with hemophilia A with or without inhibitors. Results from both
studies will be presented as late-breaking abstracts.

“The results from HAVEN 3 study demonstrate that HEMLIBRA, which was
created with Chugai’s proprietary antibody engineering technologies, can
reduce the bleeding risk in people with hemophilia A without inhibitors.
The intra-patient comparison in this study also shows a statistically
significant reduction in bleeding by HEMLIBRA prophylaxis compared to
factor VIII therapy, the current standard treatment,” said Chugai’s
President & CEO, Tatsuro Kosaka. “In addition, HAVEN 4 data indicates
that regardless of the presence of inhibitors, HEMLIBRA administration
once every four weeks can reduce the risk of bleeding in people with
hemophilia A compared with existing treatments. We will closely work
with Roche to obtain approval of HEMLIBRA for the treatment of
hemophilia A without inhibitors as early as possible.”

HAVEN 3 Study

Study description

HAVEN 3 study is a randomized, multicentre, open-label phase III study
evaluating the efficacy, safety and pharmacokinetics of HEMLIBRA
prophylaxis subcutaneous injection once a week and once every two weeks.
The study enrolled 152 patients with hemophilia A, 12 years of age or
older without inhibitors to factor VIII, who were previously treated
with episodic or prophylactic factor VIII therapy.

Primary endpoint: number of treated bleeds over time with HEMLIBRA
prophylaxis (Arm A and Arm B) versus no prophylaxis (Arm C).

There were no unexpected or serious adverse events (AEs) related to
HEMLIBRA and most common AE profiles appeared consistent with the
known safety profile of the medicine.

0.0001)>

HAVEN 4 Study

Study Description

HAVEN 4 study is a single-arm, multicentre, open-label, phase III study
evaluating the efficacy, safety, and pharmacokinetics of subcutaneous
administration of HEMLIBRA dosed every four weeks. The study included 48
patients (12 years of age or older) with hemophilia A with or without
inhibitors to factor VIII who were previously treated with either
on-demand or prophylactic factor VIII or bypassing agents, depending on
their inhibitor status.

Patients with or without inhibitors to factor VIII previously treated
with either on-demand or prophylactic factor VIII or bypassing agents
were enrolled in two cohorts. The study was conducted in two stages as
follows;

Cohort

Objective

Treatment Regimen

Pharmacokinetic (PK) run-in cohort

(n=7)

Evaluate pharmacokinetics

Received HEMLIBRA prophylaxis at 6 mg/kg once every 4 weeks

Expansion cohort

(n=41)

Evaluate efficacy and safety

Received HEMLIBRA prophylaxis at 3 mg/kg once every week for 4
weeks, followed by 6 mg/kg once every 4 weeks

All patients in the PK run-in cohort (n=7) were previously treated with
on-demand treatment and then received HEMLIBRA prophylaxis in the study.
The evaluation of pharmacokinetics was conducted after monitoring all
seven patients in the PK run-in cohort for at least six weeks since they
had initiated the administration of HEMLIBRA, followed by an expansion
cohort study. Episodic treatment of breakthrough bleeds with factor VIII
therapy was allowed per protocol.

Results from HAVEN 4 study is consistent with results obtained from
other phase III studies of HEMLIBRA. These data show that once every 4
weeks prophylaxis of HEMLIBRA can provide clinically meaningful
control of bleeding in patients with hemophilia A with or without
factor VIII inhibitors.

There were no unexpected or serious adverse events (AEs) related to
HEMLIBRA and the most common AEs were consistent with previous studies.

Injection site reaction was the most common AE, occurring in nine
people.

Summary of the HAVEN 3 (NCT02847637) study results presented at
WFH

Study Description

A randomized, multicentre, open-label phase III study evaluating the
efficacy, safety and pharmacokinetics of HEMLIBRA prophylaxis
subcutaneous injection once a week and once every two weeks.

Patients

Patients with hemophilia A, 12 years of age or older without
inhibitors to factor VIII, who were previously treated with
episodic or prophylactic factor VIII therapy.

N=152

Primary endpoint

Number of bleeds over time with HEMLIBRA prophylaxis (Arm A and Arm
B) versus no prophylaxis (Arm C)

Study group

No prophylaxis

(Arm C; n=18)

Once weekly HEMLIBRA prophylaxis

(Arm A; n=36)

Once every 2 weeks HEMLIBRA prophylaxis

(Arm B; n=35)

Treated bleeds (primary endpoint)

Median efficacy period, weeks

(min–max)

24.0

(14.4–25.0)

29.6

(17.3–49.6)

31.3

(7.3–50.6)

Model-based ABR (95% CI)*

38.2

(22.9; 63.8)

1.5

(0.9; 2.5)

1.3

(0.8; 2.3)

% reduction vs arm C

(RR, Wald test; p-value)

N/A

96% reduction

(0.04, p <0.0001) p>
0.0001)>

97% reduction

(0.03, p <0.0001) p>
0.0001)>

Median ABR

(Interquartile range; IQR)

40.4

(25.3; 56.7)

0.0

(0.0; 2.5)

0.0

(0.0; 1.9)

% patients with zero bleeds

(95% CI)

0.0

(0.0; 18.5)

55.6

(38.1; 72.1)

60

(42.1; 76.1)

% patients with zero to three bleeds

(95% CI)

5.6

(0.1; 27.3)

91.7

(77.5; 98.2)

94.3

(80.8; 99.3)

Treated bleeds ABR intra-patient comparison

(Arm D patients who participated in NIS, n=48; secondary
endpoint)

Study group

Prior factor VIII prophylaxis

(Arm C; n=48)

Once-weekly HEMLIBRA prophylaxis

(Arm D; n=48)

Median efficacy period, weeks

(min–max)

30.1

(5.0–45.1)

33.7

(20.1–48.6)

Model-based ABR*

(95% CI)

4.8

(3.2; 7.1)

1.5

(1.0; 2.3)

% reduction vs NIS Factor VIII

(RR, p-value)

68% reduction

(0.32, p <0.0001) p>
0.0001)>

Median ABR (IQR)

1.8

(0.0; 7.6)

0.0

(0.0; 2.1]

% patients with zero bleeds

39.6

(25.8; 54.7)

54.2

(39.2; 68.6)

% patients with zero to three bleeds

72.9

(58.2; 84.7)

91.7

(80.0; 97.7)

*Negative binomial regression model

Summary of the HAVEN 4 (NCT03020160) study results presented at
WFH

Study Description

A single-arm, multicentre, open-label, phase III study evaluating
the efficacy, safety, and pharmacokinetics of subcutaneous
administration of HEMLIBRA dosed every four weeks.

Patients

12 years of age or older patients with hemophilia A with or
without inhibitors to factor VIII who were previously treated with
either on-demand or prophylactic factor VIII or bypassing agents,
depending on their inhibitor status.
N=48

Primary endpoint

bleed rate with HEMLIBRA prophylaxis

Study group

HEMLIBRA prophylaxis (n=48 total; n=41 included in efficacy analyses)

Treated bleeds (primary endpoint)

ABR, model based

(95% CI)

2.4

(1.4; 4.3)

Median ABR,

calculated

(IQR)

0.0

(0.0; 2.1)

% patients with zero bleeds

(95% CI)

56.1

(39.7; 71.5)

% patients with zero to three bleeds

(95% CI)

90.2

(76.9; 97.3)

About Chugai

Chugai Pharmaceutical is one of Japan’s leading research-based
pharmaceutical companies with strengths in biotechnology products.
Chugai, based in Tokyo, specializes in prescription pharmaceuticals and
is listed on the 1st section of the Tokyo Stock Exchange. As an
important member of the Roche Group, Chugai is actively involved in R&D
activities in Japan and abroad. Specifically, Chugai is working to
develop innovative products which may satisfy the unmet medical needs,
mainly focusing on the oncology area.
In Japan, Chugai’s research
facilities in Gotemba and Kamakura are collaborating to develop new
pharmaceuticals and laboratories in Ukima are conducting research for
technology development for industrial production. Overseas, Chugai
Pharmabody Research
based in Singapore is engaged in research
focusing on the generation of novel antibody drugs by utilizing Chugai’s
proprietary innovative antibody engineering technologies. Chugai
Pharma USA
and Chugai
Pharma Europe
are engaged in clinical development activities in the
United States and Europe.
The consolidated revenue in 2016 of
Chugai totalled 491.8 billion yen and the operating income was 80.6
billion yen (IFRS Core basis).
Additional information is available
on the internet at https://www.chugai-pharm.co.jp/english
.